Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23)

A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo- controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase- type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.     

Identification of SPARC-like 1 protein as part of a biomarker panel for Alzheimer's disease in cerebrospinal fluid

We have used proteomic fingerprinting to investigate diagnosis of Alzheimer's disease (AD). Samples of lumbar cerebrospinal fluid (CSF) from clinically-diagnosed AD cases (n = 33), age-matched controls (n = 20), and mild cognitive impairment (MCI) patients (n = 10) were used to obtain proteomic profiles, followed by bioinformatic analysis that generated a set of potential biomarkers in CSF samples that could discriminate AD cases from controls. The identity of the biomarker ions was determined using mass spectroscopy. The panel of seven peptide biomarker ions was able to discriminate AD patients from controls with a median accuracy of 95% (sensitivity 85%, specificity 97%). When this model was applied to an independent blind dataset from MCI patients, the intensity of signals was intermediate between the control and AD patients implying that these markers could potentially predict patients with early neurodegenerative disease. The panel were identified, in order of predictive ability, as SPARC-like 1 protein, fibrinogen alpha chain precursor, amyloid-β, apolipoprotein E precursor, serum albumin precursor, keratin type I cytoskeletal 9, and tetranectin. The 7 ion ANN model was further validated using an independent cohort of samples, where the model was able to classify AD cases from controls with median accuracy of 84.5% (sensitivity 93.3%, specificity 75.7%). Validation by immunoassay was performed on the top three identified markers using the discovery samples and an independent sample cohort which was from postmortem confirmed AD patients (n = 17).     

Pediatric patients with achondroplasia: CT evaluation of the craniocervical junction

Twenty-six patients (4 months to 6 years old) with achondroplasia complicated by sleep apnea and/or other neurologic manifestations underwent plain computed tomography (CT) of the craniocervical junction; six also underwent CT myelography. For objectification, multiplanar reconstruction was used to complement axial plane measurements by providing coronal and sagittal measurements; multiplanar reconstruction also improved perception of the longitudinal relationships between the brain stem and subarachnoid space. A narrow subarachnoid space was found in all 26 patients; marked cord compression was present in nine, six of whom underwent CT myelography. These six had marked focal obliteration of the subarachnoid space on both plain CT and CT myelography. Since the subarachnoid space immediately above and below the craniocervical junction is normally capacious, when marked constriction was present, no additional information could have been gained from CT myelography. Thus, plain CT was shown to be sufficient for surgical planning (suboccipital decompression) in nine patients with cord compression due to achondroplasia.     

The effect of exchange therapy on postburn lymphocyte suppression

Circulating mediators have been implicated in the pathophysiology of postburn immunologic depression, suggesting the restorative potential of exchange therapy. Previous reports have stressed the immunosuppressive effects of massive transfusions and major surgical procedures. The effect of plasma exchange (PLA/EX) and surgical excision and grafting (E/G) procedures on postburn lymphocyte function was evaluated retrospectively in one-way mixed lymphocyte reaction assays. Twenty one adult patients with a mean total body surface area (TBSA) burn of 52.6% underwent a total of 54 PLA/EX procedures without complications. The mean volume of plasma exchanged was 5079 ml. PLA/EX was performed at a mean time of 10.4 days after burn injury. Thirty adult patients with a mean TBSA burn of 42.8% underwent a total of 78 E/G procedures. The mean graft size was 2373 cm2 per E/G procedure or 7.25% TBSA. The mean transfusion requirement per E/G was 3355 ml. The initial E/G occurred at a mean of 7.5 days after burn injury. PLA/EX decreased suppression of normal lymphocyte blastogenesis by burn serum from 62.7% to 28.3% (p less than 0.001). The mean duration of improvement in lymphocyte function was 4.8 days. Similarly, the mean suppression by burn serum drawn pre-E/G was 42.2%, while serum suppressive activity post-E/G was 29.1% (p less than 0.05). The mean duration of mixed lymphocyte reaction improvement was 5.0 days. Both PLA/EX and E/G procedures have a significant beneficial effect in restoring lymphocyte function in burn patients.     

Persistent prolongation of simple reaction time in sports concussion

A baseline computerized cognitive assessment was completed by 483 military cadets before their initial school year. Fourteen cadets concussed during physical education boxing were retested <1 hour after injury and again on return to full activity 4 days later. Compared with baseline testing, postinjury performance on simple reaction time and continuous performance tests was significantly slowed, even after cadets experienced resolution of physical symptoms and were cleared to resume full activity. These findings may be relevant to current concussion management guidelines.